Bradley J. Monk, MD, FACOG, FACS: The second category of FDA approved targeted therapies in ovarian cancer have been inhibitors of poly ADP ribose polymerase, which we call PARP. In fact, there are 3 FDA approved PARP inhibitors in 6 different indications, and I promise you there are more to come. We’ve been talking about the frontline treatment of ovarian cancer and how the addition of bevacizumab to carboplatin/paclitaxel is a good option and is, indeed, FDA approved, particularly in the sickest patients. But now we have a frontline biomarker. Dr Moore, thank you for your passion in SOLO-1, presented at ESMO [the European Society for Medical Oncology annual meeting], published in the New England Journal of Medicine, and FDA approved December 19th. Tell us about SOLO-1.
Kathleen N. Moore, MD: SOLO-1 was a randomized phase III study that allowed women with a BRCA mutation, advanced ovarian cancer, excellent performance status, at least an attempt at cytoreduction, either primary or interval, and importantly, either a complete or partial response to frontline chemotherapy to finish their chemotherapy and then be randomized in a 2:1 fashion to receive olaparib tablets twice daily or placebo. They continued their assigned therapy until disease progression. And if that didn’t occur, they stopped at 2 years; unless at 2 years there was some evidence of disease, CA-125 [cancer antigen 125] elevation, or something for which the provider felt like the patient should stay on their assigned treatment. And with appeal to the medical monitor or me, they could do so.
The primary endpoint was investigator-assessed progression-free survival, and there were a number of secondary endpoints inclusive of overall survival and quality of life endpoints. The arms are very well balanced, and importantly, did represent ovarian cancer in general. About 30% of patients had neoadjuvant chemotherapy, but 70% had primary cytoreduction. And of those, over 70% were debulked per the surgeon’s report to no gross residual, and 80% were stage III versus stage IV. So this is a really good prognostic group of patients.
Bradley J. Monk, MD, FACOG, FACS: Median age of 53. Most had great surgery, and they’re all BRCA.
Kathleen N. Moore, MD: And they’re all BRCA.
Bradley J. Monk, MD, FACOG, FACS: We should cure those without olaparib.
Kathleen N. Moore, MD: That’s the myth of BRCA.
Bradley J. Monk, MD, FACOG, FACS: But we don’t.
Kathleen N. Moore, MD: That’s the myth. That’s what people thought. And this is a group that’s excluded from every study now because they’re so low risk, which we need to stop saying. So very well balanced. What we showed in the primary analysis was, at the data cut point we hadn’t even reached the median in the olaparib group. In the placebo group, the median was 13.8 months. By 6 months, 20% of the placebo had progressed. By a year, 50% of the placebo group had progressed. And by 3 years, 27% of the placebo group were disease-free—only 27% versus 63% in the olaparib group. So the hazard ratio between the curves, even though we don’t have a median, was 0.3. So a 70% reduction in the risk of progression. And if you look at our sensitivity analyses, the estimate for the median progression-free survival for olaparib is somewhere between 47 and 50 months.
Bradley J. Monk, MD, FACOG, FACS: Three years difference.
Kathleen N. Moore, MD: Three years difference. And certainly, you can access the paper and see the curves, but the shape of the curve on the olaparib group is unlike any curve we’ve shown in ovarian cancer to date, in that it flattens. It flattens and that shape is maintained beyond the 2-year stop point. Unlike bevacizumab, where you stop at 15 months and then start to tail off, here you stop and just keep right on not progressing.
Bradley J. Monk, MD, FACOG, FACS: Said another way though, the shape of the curve early on is very steep.
Kathleen N. Moore, MD: Very steep.
Bradley J. Monk, MD, FACOG, FACS: You said in the placebo arm it was 50% at 12 months. And so, even in the olaparib group it’s steep and then there’s a tail. Maybe there are more cures?
Kathleen N. Moore, MD: That’s what we hope. We can’t say that yet.
Bradley J. Monk, MD, FACOG, FACS: I know.
Kathleen N. Moore, MD: But we hope there are more cures.
Bradley J. Monk, MD, FACOG, FACS: So Elena, has this changed your practice?
Elena S. Ratner, MD: Oh my gosh, yes. PARP inhibitors in general completely changed my practice. I was excited about it in the recurrent setting, but this changes the entire disease management. I think this curve means that, potentially, for the first time, we can actually increase cure, which we’ve never been able to do.
Bradley J. Monk, MD, FACOG, FACS: And you mentioned stem cells. Maybe there’s an interaction there.
Transcript Edited for Clarity